Moderate alcohol consumption has been associated with a reduction in the risk of CHD. These beneficial effects are most commonly attributed to alcohol-induced changes in lipids, although the mechanisms underlying the cardioprotective effects of low to moderate alcohol consumption are unknown. Lipid levels are influenced by multiple factors, including environmental (e.g. alcohol) and genetic factors, and while the independent effects of each of these factors on lipids have been widely studied, their combined effects have been less studied and are less understood. Previous studies have primarily utilized a candidate gene approach to investigate pre-selected genetic variation within lipid metabolism genes; however, advances in polymorphism discovery, population genetics and genotyping technologies have yielded a genome-wide collection of SNPs that span the human genome. Therefore, it is now possible (and more plausible) to utilize a genome-wide association approach to identify gene-alcohol interactions influencing lipids. The ARIC study [N~16,000] has been genotyped for >1,000,000 SNPs spanning the human genome, and the proposed research will leverage the full scope of this resource to identify gene-alcohol interactions influencing lipd levels, with replication facilitated through pre-arranged collaborations with the CARDIA Study [N~3,750] and the Dallas Heart Study [N~3,550]. Further genotyping of functional variants and/or TagSNPs within the genes/regions of the top replicated hits will aid in our identification o putative functional variants that specifically interact with alcohol consumption to influence lipid levels. PUBLIC HEALTH RELEVANCE: Moderate alcohol consumption has been associated with a reduction in the risk of CHD, most notably through the beneficial effects of alcohol on lipids. Previous studies have primarily utilized a candidate gene approach to investigate pre-selected genetic variation within lipid metabolism genes; however, it is now possible (and more plausible) to use a genome-wide association approach to identify gene-alcohol interactions influencing lipids. The ARIC study has been genotyped for >1,000,000 SNPs spanning the human genome, and the proposed research will leverage the full scope of this available resource (as well as two independent replication cohorts, CARDIA and DHS) to identify gene-alcohol interactions influencing lipid levels. Further genotyping of functional variants and/or TagSNPs within the genes/regions of the top replicated hits will aid in the identification of putative functional varints that specifically interact with alcohol consumption to influence lipid levels.